Role of macrophage tissue infiltration in obesity and insulin resistance

Bourlier, Virginie; Bouloumié, Anne

doi:10.1016/j.diabet.2009.05.001

Cited by 115 publications

(87 citation statements)

References 109 publications

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“…We speculate that the presence of abnormal adipose tissue is largely due to reduced macrophage infiltration in CatE -/-mice. It is known that the maturation process from pre-adipocyte to adipocyte is predominantly sustained by infiltration and interaction of macrophages and immune-related cells [15,16]. Moreover, the fact that cathepsin E is hardly detected in adipocytes but is highly 8 expressed in macrophages further supports our notion.…”

Section: Discussionsupporting

confidence: 82%

Defective adipose tissue development associated with hepatomegaly in cathepsin E-deficient mice fed a high-fat diet

Kadowaki

Kido

Hatakeyama

et al. 2014

Biochemical and Biophysical Research Communications

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Running title: Fat-induced cathepsin E-deficient mice Key words: cathepsin E, high-fat diet, adipose tissue AbstractCathepsin E is an intracellular aspartic proteinase, which is predominantly distributed in immune-related and epithelial cells. However, the role of the enzyme in adipose tissues remains unknown. In this study, we investigated the characteristics of cathepsin E-deficient (CatE -/-) mice fed a high-fat diet (HFD), as a mouse model of obesity. HFD-fed CatE -/-mice displayed reduced body weight gain and defective development of white adipose tissue (WAT) and brown adipose tissue (BAT), compared with HFD-fed wild-type mice. Moreover, fat-induced CatE -/-mice showed abnormal lipid accumulation in non-adipose tissues characterized by hepatomegaly, which is probably due to defective adipose tissue development. Detailed pathological and biochemical analyses showed that hepatomegaly was accompanied by hepatic steatosis and hypercholesterolemia in HFD-induced CatE -/-mice. In fat-induced CatE -/-mice, the number of macrophages infiltrating into WAT was significantly lower than in fat-induced wild-type mice. Thus, the impaired adipose tissue development in HFD-induced CatE -/-mice was probably due to reduced infiltration of macrophages and may lead to hepatomegaly accompanied by hepatic steatosis and hypercholesterolemia.

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Section: Discussionsupporting

confidence: 82%

Defective adipose tissue development associated with hepatomegaly in cathepsin E-deficient mice fed a high-fat diet

Kadowaki

Kido

Hatakeyama

et al. 2014

Biochemical and Biophysical Research Communications

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“…Importantly, it should be recognised that the current classification is imprecise and that there is a need for it to be expanded to encompass a spectrum of macrophage populations with different shades of activation [21]. However, according to the current nomenclature, our data are in agreement with a remodelling phenotype for human ATM expressing pro-and anti-inflammatory markers [22,47]. These M2-like genes showed increased expression in SAT and VAT in the metabolic syndrome compared with lean individuals and were correlated with variables of adiposity and the metabolic syndrome.…”

Section: Discussionsupporting

confidence: 80%

Macrophage gene expression is related to obesity and the metabolic syndrome in human subcutaneous fat as well as in visceral fat

et al. 2011

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Aims/hypothesis Our goal was to identify a set of human adipose tissue macrophage (ATM)-specific markers and investigate whether their gene expression in subcutaneous adipose tissue (SAT) as well as in visceral adipose tissue (VAT) is related to obesity and to the occurrence of the metabolic syndrome. Methods ATM-specific markers were identified by DNA microarray analysis of adipose tissue cell types isolated from SAT of lean and obese individuals. We then analysed gene expression of these markers by reverse transcription quantitative PCR in paired samples of SAT and VAT from 53 women stratified into four groups (lean, overweight, obese and obese with the metabolic syndrome). Anthropometric measurements, euglycaemic-hyperinsulinaemic clamp, blood analysis and computed tomography scans were performed. Results A panel of 24 genes was selected as ATM-specific markers based on overexpression in ATM compared with other adipose tissue cell types. In SAT and VAT, gene expression of ATM markers was lowest in lean and highest in the metabolic syndrome group. mRNA levels in the two fat depots were negatively correlated with glucose disposal rate and positively associated with indices of adiposity and the metabolic syndrome. Conclusions/interpretation In humans, expression of ATMspecific genes increases with the degree of adiposity and correlates with markers of insulin resistance and the metabolic syndrome to a similar degree in SAT and in VAT.

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“…From a wide range of macrophage polarization states, the most frequently described have been M1 as 'classically activated' releasing pro-inflammatory cytokines and M2 as 'alternatively activated' producing anti-inflammatory cytokines. 29,[43][44][45] However, the reliable markers for M1 and M2 characterization in human AT are still not clearly defined. Most results come from in vitro or animal experiments and only a limited number of human studies solve this problem.…”

Section: Discussionmentioning

confidence: 99%

“…The differences between human and mouse macrophages including ATM is well documented. 10,29,50 A recent study investigating human ATM phenotype by immunohistochemistry analysis reported that the M1/M2 ratio shifted in favor of M2 status 3 months after gastric surgery. 51 This study investigated class III morbidly obese subjects and used single markers to calculate numbers of M1 and M2 macrophages, whereas we studied class I obese women after a 6-month dietary intervention and used a combination of cell surface markers specific for macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…27,28 In humans, ATMs express both M1-and M2-related markers, revealing an intermediate phenotype with inflammatory and antiinflammatory capacities. 10,29,30 Little is known regarding the stimuli that influence AT inflammation and phenotype of immune cells. One of the possible factors altering immune system could be variation in nutritional status.…”

Section: Introductionmentioning

confidence: 99%

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Dietary intervention-induced weight loss decreases macrophage content in adipose tissue of obese women

et al. 2010

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Objective: Accumulation of adipose tissue macrophages (ATMs) is observed in obesity and may participate in the development of insulin resistance and obesity-related complications. The aim of our study was to investigate the effect of long-term dietary intervention on ATM content in human adipose tissue. Design: We performed a multi-phase longitudinal study. Subjects and measurements: A total of 27 obese pre-menopausal women (age 39±2 years, body mass index 33.7±0.5 kg m -2 ) underwent a 6-month dietary intervention consisting of two periods: 4 weeks of very low-calorie diet (VLCD) followed by weight stabilization composed of 2 months of low-calorie diet and 3to 4 months of weight maintenance diet. At baseline and at the end of each dietary period, samples of subcutaneous adipose tissue (SAT) were obtained by needle biopsy and blood samples were drawn. ATMs were determined by flow cytometry using combinations of cell surface markers. Selected cytokine and chemokine plasma levels were measured using enzyme-linked immunosorbent assay. In addition, in a subgroup of 16 subjects, gene expression profiling of macrophage markers in SAT was performed using real-time PCR. Results: Dietary intervention led to a significant decrease in body weight, plasma insulin and C-reactive protein levels. After VLCD, ATM content defined by CD45 þ /14 þ /206 þ did not change, whereas it decreased at the end of the intervention. This decrease was associated with a downregulation of macrophage marker mRNA levels (CD14, CD163, CD68 and LYVE-1 (lymphatic vessel endothelial hyaluronan receptor-1)) and plasma levels of monocyte-chemoattractant protein-1 (MCP-1) and CXCL5 (chemokine (C-X-C motif) ligand 5). During the whole dietary intervention, the proportion of two ATM subpopulations distinguished by the CD16 marker was not changed. Conclusion: A 6-month weight-reducing dietary intervention, but not VLCD, promotes a decrease in the number of the whole ATM population with no change in the relative distribution of ATM subsets.

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Role of macrophage tissue infiltration in obesity and insulin resistance

Cited by 115 publications

References 109 publications

Defective adipose tissue development associated with hepatomegaly in cathepsin E-deficient mice fed a high-fat diet

Defective adipose tissue development associated with hepatomegaly in cathepsin E-deficient mice fed a high-fat diet

Macrophage gene expression is related to obesity and the metabolic syndrome in human subcutaneous fat as well as in visceral fat

Dietary intervention-induced weight loss decreases macrophage content in adipose tissue of obese women

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